An infection occurs when bacteria invade and multiply inside a living body and the body exhibits disease symptoms, and once bacteria begin to multiply in the body, the body reacts in a variety of ways, and various symptoms such as redness and swelling appear. Use of drugs such as antibiotics is appropriate at this point, and helps to cure the infection. However, when it is too late to use antibiotics, or when their use is inappropriate, or when use is interrupted in the course of therapy, or when enough of the drug cannot get to the infection, reduction or removal of the pathogen is prevented and treatment is ultimately unsuccessful in many cases. In addition, problems have recently risen affecting both the bacteria and their hosts, complicating circumstances so that infections last longer or are more severe and difficult to treat.
The first victory for humans in the war against infectious disease occurred in the mid-twentieth century with the advent of antibiotics, beginning with penicillin. Unlike previous drugs, this drug was hailed as a “magic bullet” for its dramatic effects: it seemed that infection had been conquered, and that the term “infectious disease” would soon be obsolete. Bacteria are not easily conquered, however, and overuse of antibiotics led to the appearance and spread of drug-resistant bacteria. Having survived and regrouped, the bacteria are on the attack again. Bacteria that have acquired resistance have succeeded in transmitting this resistance across species boundaries through the conjugation of special DNA fragments (resistance genes) called R-plasmids. As a result, medicine truly seems to be on the brink of defeat due to the prevalence and spread of methicillin-resistant Staphylococcus aureus (MRSA), a major cause of hospital-based infections, and other multidrug-resistant bacteria including vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa, Mycobacterium tuberculosis, Shigella flexneri and the like.
For example, 80% of adults are said to suffer from periodontal disease, in which surrounding tissues that support the teeth including the gums, cement, periodontal ligaments, alveolar bone and the like become inflamed and are gradually destroyed. This is caused by bacteria that preferentially colonize and form plaque in the periodontal tissue, particularly grooves in the cervical part at the boundary between the teeth and gums. The gums become locally inflamed due to toxins and enzymes produced by these bacteria, resulting in gingivitis, and as this progresses gum pockets form where plaque accumulates, resulting in periodontitis. As the symptoms progress the pockets deepen and widen, inflammation spreads to and gradually destroys the roots of the teeth, which sooner or later fall out. Specifically, in the initial stages of periodontal disease the gums of the cervical part to which plaque has attached itself become red and swollen, losing their elasticity and bleeding during brushing. If this is ignored, the plaque gradually grows and forms calculus, spreading open the cervical area to form periodontal pockets. The calculus forms a barrier which prevents brushing of the underlying plaque, so that the bacteria gain force and their toxins cause the pockets to grow larger and larger, and the inflammation spreads from the gums to the periodontal ligament and alveolar bone, causing bleeding and pus with halitosis while at the same time the infection spreads one by one to the surrounding teeth. If inflammation of the pockets becomes chronic, the alveolar bone which supports the roots of the teeth begins to dissolve from the surface, accompanied by edema of the gums, the teeth wobble and feel loose because they are not properly supported, and strong halitosis occurs along with pain when the patient bites down hard. As the disease progresses most of the alveolar bone is lost, the roots of the teeth are exposed, the teeth become looser so that the patient can no longer eat hard foods, and finally the teeth fall out one by one. Consequently, experts recognize periodontal disease as a classic model of a chronic infectious disease that is still hard to cure.
Another problem concerns the drugs themselves: drugs are foreign to the body and produce side-effects to a greater or lesser degree, and experts point out that the more effective the drug, the greater the side-effects. In general it is said that the effects of drugs are halved while the side effects are doubled in the elderly—a fact that cannot be ignored considering the aging of society. The stronger and stronger demands for safety and security from society as a whole also cannot be ignored. Accidental deaths from side effects continue to occur. Antibiotics are no exception, in fact producing much stronger blood toxicity than other drugs including the allergic reaction called “penicillin shock” as well as leucopenia, anemia and the like, and the resulting loss of immune strength has been recognized at public institutions. Because antibiotics are so useful, however, this has not been much of a problem except in actual cases of severe illness or death.
Antibiotics have another side effect which is not immediately obvious: they attack the intestinal flora, which is sometimes called a vital organ, causing microbial substitution. That is, immune function is further depressed by the synergistic effect of blood toxicity combined with a decrease in beneficial intestinal bacteria that are highly sensitive to antibiotics, promoting chronic infections and leading to new viral diseases and other infections. In fact, the bacteria which cause typical chronic infections such as periodontal disease, sinusitis, hemorrhoids and the like are often antibiotic resistant, and side effects accumulate while the drug is ineffective. Even without resistance, the more an antibiotic is used, the greater the risk of mutation into resistant strains. On the individual level, continuous exposure to toxins from pathogenic bacteria can be fatal when combined with decreased immune function, while on a societal level resistant bacteria have crossed national boundaries to cause unanticipated harm throughout the world.
Looking at the United States and Europe, the idea of creating bodies which do not become sick rather than treating them when they become sick (preventive medicine) has been in force for over a decade, and one effective means for this when has been accepted because of its safety is “probiotics,” which borrows the help of beneficial bacteria.
Research into Lactobacillus was started in France by Pasteur, the father of modern microbiology, leading to the “prolongation of life” theory of the Russian Metchinikoff and many subsequent clinical applications, but it still has not been put into true practical use. This is because the results of epidemiological studies have not matched the results of experimental research. Recently, however, advances in intestinal bacteriology have shown that Lactobacillus has the following important roles.
(1) Immune function normalization: Normalizes and enhances the immune function, which is indispensable for maintaining life
(2) Intestinal cleansing: Balances the intestinal flora, suppresses proliferation of harmful bacteria, and suppresses abnormal fermentation and production of harmful bacteria in the intestines
(3) Blood cleansing: cleanses the blood as an extension of the intestinal cleansing function
(4) Promotion of food utilization: Promotes synthesis of vitamins and amino acids; aids absorption of nutrients through the intestinal walls
(5) Prevention of infections by harmful bacteria: prevents proliferation and infection in the intestine even if harmful bacteria invade from the outside
(6) Cell normalization: Promotes normalization of cell functions
In Japan as well, as society ages and controlling health costs becomes a national concern, the importance of disease prevention is being recognized and society as a whole is becoming more concerned with health. As a result, the number of products containing Lactobacillus as an ingredient is rising steadily, and more and more so-called “functional yoghurt” products are being developed. However, the truth is that if these product are consumed intermittently, effects such as those mentioned in (1) through (6) above and other definite effects on disease will be few and far between, while actual effectiveness against infection would seem to be a fool's hope.
Under these circumstance, the inventors proposed that a lactic acid bacillus having unique properties which was isolated and selected by the inventors in May of 2000 be used against infections with the aim of resolving the ill effects of conventional antibiotics such as drug-resistant bacteria, drug allergies, side-effects and problems affecting ordinary bacterial flora, and submitted a patent application for a “New Lactic Acid Bacterium Effective on Infectious Disease and Lactobacillus Preparation Comprising Lactic Acid Bacterium as Main Ingredient” (Japanese Patent Application Laid-open No. 2001-333766).
This application relates to a lactic acid bacillus which is a Lactobacillus casei species that not only acts to inhibit the growth of pathogenic bacteria but also produces “novel bioactive substances” which have the property of weakening the toxicity of pathogenic bacteria, and to a Lactobacillus preparation for acute and chronic infections which has this bacterium as a main component. In detail, of the Lactobacillus casei collected from nature we selected only those strains producing a broad-spectrum antibiotic, and then screened for hemolytic and S-R mutations, with confirmation through animal testing, to determine whether or not that antibiotic weakened the toxicity of pathogenic bacteria, and finally three strains of Lactobacillus casei which met the criteria, FERM BP-6771, FERM BP-6772 and FERM BP-6773, were applied to infections. These were also given resistance to widely-used antibiotics so that they could be used in combination with those antibiotics. In cases of acute infections such as acute colitis, acute cystitis, acute bronchitis and the like, faster treatment effects were achieved through use of these Lactobacilli in conjunction with antibiotic administration than were achieved with conventional antibiotics alone, including (i) reduced antibiotic dosage, (ii) quicker amelioration of symptoms and faster recovery with fewer side-effects, and (iii) less disturbance of the intestinal flora, and the ill effects from the drug were reduced. However, the effects took time to appear and a complete cure was not achieved in the case of chronic infections such as gingivitis, sinusitis, bronchitis and hemorrhoids.
As discussed above, the issue is to grow a Lactobacillus casei capable of colonizing and multiplying in the lesions of a chronic infection that resists treatment, and of providing a strong cleansing action while eliminating the causal bacteria.